System and method for testing visual capability and for assessing ocular toxicity and ocular effects of bio-effective materials

ABSTRACT

An automated system for assessing the visual capability of a human subject under a wide range of optical environmental conditions including low illumination, glare, low and high contrast, and off axis events, which, used over time during the administration of a bio-effective compound, permits even subtle changes in visual capability of a subject to be detected.

FIELD OF THE INVENTION

[0001] The present invention pertains to automated systems for assessingthe visual capability of a human subject under a wide range of opticalenvironmental conditions including low illumination, glare, low and highcontrast, and events off the central axis of the field of vision. Usedover time during the administration of a bio-effective compound, evensubtle changes in visual capability of a subject may be detected.

BACKGROUND OF THE INVENTION

[0002] Methods of assessing acuity at the axis of fixation, such as theSnellen or Lovie-Bailley charts have been used for almost 150 years inorder to determine the relative performance of a human subject's vision.Results of these tests are reported as a fraction such as 20/20, wherethe numerator represents the 20 foot visual acuity of the human subject,and the denominator represents the distance at which a normal humansubject is also able to discern the same letter size. Thus, 20/200 isinterpreted to mean that what the test subject sees at 20 feet, anaverage person can distinguish at 200 feet from the object. Conversely,20/10 is interpreted to mean that the subject has hyper-acuity; as whata normal person sees at ten feet, the subject sees at 20. This systemonly measures high contrast acuity without color evaluation, and only inthe central one degree of vision under one illumination condition thatis not controlled. It is insensitive to subtle changes in the refractingmedium or retinal or neural perception. Similarly, contrast sensitivityusing Nyquist sinusoidal grating measures non-discriminative targets inthe central four degrees of vision under one illumination level.

[0003] U.S. Pat. No. 5,589,897, entitled “Method and apparatus forcentral visual field mapping and optimization of image presentationbased upon mapped parameters” teaches a method and apparatus provides amuch more precise and accurate measurement of a human subjects visualcapability across a wide region of the visual field. The disclosure andclaims of that patent are incorporated herein by reference.

[0004] It is generally known that many bio-effective compounds inducechanges in visual capability. In the medical literature, for example,the compound chloroquine was shown to be toxic to the retina, althoughthis side effect of the drug was not well understood until after manypatients had lost their sight. Because of such effects, the UnitedStates Food and Drug Administration requires that all new drugcandidates be screened for clinical evidence of ocular toxicity. Methodsfor such screening, including the central chart acuity, contrastsensitivity, and color vision testing (Farnsworth DI5 panel), however,are often inadequate, and fail to quantify subtle changes occurring overlong time periods, in perception areas off the central axis. Humphreyautomated field testing is not commonly used, nor does it utilizediscriminated targets and tests only under one level of illumination.

BRIEF DESCRIPTION OF THE INVENTION

[0005] The present invention comprises in combination, a general purposedigital computer system having a display screen and a directional userinput device, and special purpose software for displaying visual stimuliand recording user response input about them. This system is employedover time to provide a longitudinal record of the visual capabilities ofa subject, and to allow recognition of changes and trends in such visualcapabilities.

DETAILED DESCRIPTION OF THE INVENTION

[0006] Visual acuity is usually tested in the central visual field bytesting the ability of a human subject to discern a variety of letterson a wall chart, mounted at a standard distance from the subject, withstandard illumination. Such tests, therefore, require the services of atechnician to listen to the test subject and interpret his/her responsesin a non-standardized method that varies with response and technicianinterpretation. In the system of the present invention, the letter “C”is presented in one of four orientations (facing with the open segmentup, down, left or right) and the direction of the orientation isindicated by the test subject using a directional input device connectedto the computer system (for instance, a common game pad having adiamond-shaped array of four button switches.) In the present system,the letter “C” is presented in progressively larger and smaller sizes,and varying levels of luminance and in varying combinations of hue andsaturation, against backgrounds that are also varied in luminance, hue,and saturation. In this way, visual acuity (ability to discriminatetargets at central fixation) may be measured in many dimensions such asspatial acuity, contrast acuity (luminance differential under conditionsof low, normal, and high illumination), color contrast acuity (abilityto distinguish among various hues), and color sensitivity (ability todistinguish among various saturations of the same or similar hues.) Inaddition, when using a fixation target, the ability of the test subjectmay be optionally monitored using an optical fixation system (such asthat available from Iscan, Inc.), and more than just the central visualfield may be tested. Typically, the central field can be measured atmultiple intercepts (25 to 90) in the central twenty degrees of vision.

[0007] The system of the present invention is employed beforeadministration of a bio-effective compound to test the subject and toestablish a baseline of visual capability for that subject. Thereafter,the bio-effective compound is administered, and after one or moreintervals, the subject is re-tested using the system of the presentinvention, and the results compared with one or more previous results.Changes and trends may thus be presented and analyzed.

[0008] While the invention has been described in its preferredembodiments, it is to be understood that the words which have been usedare words of description rather than of limitation and that changes maybe made within the purview of the appended claims without departing fromthe true scope and spirit of the invention in its broader aspects. Theinventor further requires that the scope accorded his claims be inaccordance with the broadest possible construction available under thelaw as it exists on the date of filing hereof, and that no narrowing ofthe scope of the appended claims be allowed due to subsequent changes inthe law, as such a narrowing would constitute an ex post facto law, anda taking without due process or just compensation.

1. A method for longitudinal assessment of ocular toxicity of a compoundto which a human subject is exposed comprising the steps of: a. Testingat least the central visual capability of the human subject prior toexposure to the compound, wherein the test assesses the subject'scapability under conditions of high glare, low illumination, highcontrast, low contrast, color contrast and saturation contrast; b.Testing at least the central visual capability of the human subjectperiodically during and after exposure to the compound; and c. Comparingthe results of the at least two of the tests to determine whether thesubject's visual capability has been affected.
 2. The method of claim 1wherein the testing of visual capability includes a region of at least 5degrees outside of the central visual field.
 3. The method of claim 1wherein the testing of visual capability includes a region of at least10 degrees outside of the central visual field.
 4. The method of claim 1wherein the testing of visual capability comprises the exposure of thehuman subject to a visual display of a plurality of differently orienteddirectional figures, and the human subject is required to indicate thedirectional orientation of each of the figures by direct input to adigital computer.
 5. The method of claim 4 wherein the directionalfigures are presented in a plurality of sizes.
 6. The method of claim 4wherein the directional figures are presented in one of a plurality ofhues, each against a background having one of a plurality of differenthues.
 7. The method of claim 4 wherein the directional figures arepresented in one of a plurality of saturations of one of a plurality ofhues, each against a background having a different saturation of thesame hue as the figure.
 8. The method of claim 1 wherein the comparisonof results comprises a comparison of each of at least a pair ofmeasurements of visual ability of the human subject, to detect changestherein.
 9. The method of claim 8 wherein the comparison also results inthe presentation of trend indications about each of the pairs ofmeasurements compared.
 10. A system for longitudinal assessment ofocular toxicity of a compound to which a human subject is exposedcomprising: a. Means for testing the visual capability of the humansubject at fixation and at a plurality of intercepts angularly distantfrom fixation, prior to exposure to the compound, wherein the testassesses the subject's capability under conditions selected from thegroup of low illumination, moderate illumination and glare illumination,high contrast, low contrast, color contrast and saturation contrast; b.Means for storing at least two results of tests conducted using themeans (a); and c. Means for comparing the results of the at least two ofthe stored tests to determine whether the subject's visual capabilityhas been affected.